Article
Multidisciplinary Sciences
Kevin C. Courtney, Jason D. Vevea, Yueqi Li, Zhenyong Wu, Zhao Zhang, Edwin R. Chapman
Summary: Studies on Synaptotagmin 1 (syt1) have shown that it plays a crucial role in synaptic vesicle exocytosis, with its self-assembling multimers being enhanced by Ca2+ and dependent on anionic phospholipids. Additionally, the juxtamembrane linker of syt1 plays a key role in exocytosis by mediating multimerization.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Ning Yin, Jingjing Zhao, Panpan Zhang, Baofu Yu, Renjie Chai, Geng-Lin Li
Summary: Hearing loss, predominantly caused by gene mutations, is a common neurosensory disorder. This study used knock-out and point mutation mice as models to investigate the synaptic changes in inner hair cells related to the complex mechanisms of MYO6 mutations. The results reveal altered exocytosis and calcium influx in both immature and mature hair cells, providing insights for the diagnosis and treatment of deafness.
CELL DEATH DISCOVERY
(2023)
Article
Neurosciences
Zhenyong Wu, Lu Ma, Nicholas A. Courtney, Jie Zhu, Ane Landajuela, Yongli Zhang, Edwin R. Chapman, Erdem Karatekin
Summary: This study aims to explore the critical features of the C2A domain of Syt1 and compare it to the analogous feature in C2B. The research found that both the poly-lysine patches in C2A and C2B contribute to membrane binding, and both are crucial for evoked release.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Benoit Delignat-Lavaud, Charles Ducrot, Willemieke Kouwenhoven, Nina Feller, Louis-Eric Trudeau
Summary: This study uncovers clear differences in the mechanisms of somatodendritic (STD) and axonal dopamine release. STD dopamine release has low capacity and differs from axonal release in terms of molecular mechanisms.
Article
Neurosciences
Takuya Hikima, Paul Witkovsky, Latika Khatri, Moses Chao, Margaret E. Rice
Summary: This study reveals the critical role of high-affinity Ca2+ sensor synaptotagmin 7 (Syt7) in somatodendritic dopamine (DA) release. Both Syt7 and Syt1 are involved in the release of DA.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Oncology
Xiao Liu, Rui Li, Xiao Chen, Jie Yao, Qingxiang Wang, Jinghong Zhang, Yuanyuan Jiang, Yiqing Qu
Summary: In this study, the researchers conducted a comprehensive pancancer analysis of SYT7, revealing its role in tumor exosome secretion and its mechanism in promoting invasion and metastasis of NSCLC cells through the activation of the mTOR signaling pathway.
Review
Biochemistry & Molecular Biology
Najeeb Ullah, Ezzouhra El Maaiden, Md Sahab Uddin, Ghulam Md Ashraf
Summary: This review focuses on the role of the Syt-1 protein in secretory vesicle docking, priming, and fusion. It highlights how Syt-1 acts as a Ca2+ sensor and participates in forming the docking complex to facilitate vesicle fusion with the plasma membrane.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2021)
Review
Neurosciences
Renhao Xue, Hao Meng, Jiaxiang Yin, Jingyao Xia, Zhitao Hu, Huisheng Liu
Summary: Exocytosis is a Ca2+-regulated process that involves the participation of Ca2+ sensors, with synaptotagmin acting as the primary sensor in the final stage of membrane fusion triggered by a Ca2+ boost. Calmodulin, on the other hand, plays a role in the earlier exocytotic steps by acting as a high affinity Ca2+ sensor. Both calmodulin and synaptotagmin play complementary roles throughout the exocytosis process.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Monica C. Quinones-Frias, J. Troy Littleton
Summary: The SYT family of proteins play crucial roles in regulating membrane trafficking at neuronal synapses, participating in synchronous and asynchronous fusion of synaptic vesicles and preventing spontaneous release. Changes in SYT isoforms can alter the fusion of synaptic vesicles and regulate trafficking of other subcellular organelles. However, the exact mechanisms by which SYTs interact with lipids and other effectors are still under investigation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Neurosciences
Daphne Atlas
Summary: Measurements have shown that synaptic vesicle fusion lags behind Ca2+-influx by approximately 60 microseconds (mu sec). The conventional model cannot explain this extreme rapidity of the release event. A recent study has found that newly tethered vesicles become fusion-competent in a Ca2+-dependent manner 300-400 ms after tethering. This confirms that Ca2+-priming and Ca2+-influx-independent fusion are two distinct events.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Neurosciences
Michael J. Seibert, Chantell S. Evans, Kevin S. Stanley, Zhenyong Wu, Edwin R. Chapman
Summary: SYT9 is a Ca2+ sensor in neuroendocrine cells, but its function in neurons is unclear. In this study, it was found that SYT9 does not trigger rapid synaptic vesicle exocytosis in mouse cortical, hippocampal, or striatal neurons unless it is overexpressed. Loss of SYT9 in striatal neurons reduced the frequency of spontaneous neurotransmitter release events. Further investigation revealed that SYT9 is localized to dense-core vesicles containing substance P, and loss of SYT9 impaired SP release, causing the observed decrease in mini frequency. The study also showed that Ca2+ binding to the C2A domain of SYT9 triggered membrane fusion in vitro, and mutations disrupting this activity abolished SYT9's ability to regulate SP release and mini frequency. Therefore, it can be concluded that SYT9 indirectly regulates synaptic transmission in striatal neurons by controlling SP release.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Physiology
Jones K. Ofori, Alexandros Karagiannopoulos, Mohammad Barghouth, Mototsugu Nagao, Markus E. Andersson, Vishal A. Salunkhe, Enming Zhang, Anna Wendt, Lena Eliasson
Summary: SYT11 and SYT13 are downregulated in islets from type 2 diabetic donors and play different roles in insulin secretion.
Article
Biochemistry & Molecular Biology
Ethiene Kwok, Shauna C. Otto, Patricia Khuu, Andrew P. Carpenter, Sara J. Codding, Patrick N. Reardon, Juan Vanegas, Tanushri M. Kumar, Chapman J. Kuykendall, Ryan A. Mehl, Joe Baio, Colin P. Johnson
Summary: Dysferlin, a large membrane protein, plays a crucial role in muscle function. It is associated with muscle diseases and its loss of activity leads to reduced exocytosis and abnormal intracellular Ca2+. In this study, the researchers found that the C2A domain of dysferlin binds preferentially to membranes containing PI(4,5)P2 through specific residues on its concave face. They also discovered that binding of the C2A domain to membranes leads to changes in lipid packing and insertion of certain residues into the membrane. These findings provide insights into the mechanism of dysferlin and its role in membrane binding and Ca2+ regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Akane Morohoshi, Haruhiko Miyata, Keizo Tokuhiro, Rie Iida-Norita, Taichi Noda, Yoshitaka Fujihara, Masahito Ikawa
Summary: Spermatozoa undergo the acrosome reaction before fusing with eggs, and the molecular mechanism of this reaction involving calcium ion (Ca2+) remains unclear. Ferlin proteins, including Fer1l5, have C2 domains that bind to Ca2+. In this study, Fer1l5 was found to be essential for male fertility, as mutant spermatozoa lacking Fer1l5 were unable to undergo the acrosome reaction even with the use of a Ca2+ ionophore. These findings suggest that FER1L5 acts as the missing link between Ca2+ and the acrosome reaction.
Article
Biology
Janus R. L. Kobbersmed, Manon M. M. Berns, Susanne Ditlevsen, Jakob B. Sorensen, Alexander M. Walter
Summary: Synaptic communication relies on the fusion of synaptic vesicles with the plasma membrane, which is achieved through the allosteric stabilization of synaptotagmin's Ca2+/PI(4,5)P-2 dual-bound state and the coordinated function of multiple synaptotagmins.
Article
Clinical Neurology
Artur Mittring, Tobias Moser, Antoine Tarquin Huet
Summary: Optogenetic control allows for innovative approaches to restore function in diseased sensory and motor systems. Customization of channelrhodopsins, emitters, and coding strategies is necessary to achieve success in clinical translation. This study provides a framework for parametrizing optogenetic neural control and applies it to the auditory pathway.
Article
Biochemistry & Molecular Biology
Chara E. S. Spanou, Alexander P. Wohl, Sandra Doherr, Annkatrin Correns, Niklas Sonntag, Steffen Luetke, Matthias Morgelin, Thomas Imhof, Jan M. Gebauer, Ulrich Baumann, Kay Grobe, Manuel Koch, Gerhard Sengle
Summary: Bone morphogenetic proteins (BMPs) play important roles in regulating cellular processes. The molecular requirements for the bioavailability of BMPs in the extracellular matrix (ECM) are not fully understood. This study shows that specific interactions of the BMPs with glycosaminoglycans (GAGs) allow for their spatial concentration in a biologically active conformation. The findings also suggest that the interaction between BMPs and GAGs is specific to certain BMPs and can protect BMPs from inactivation.
Article
Chemistry, Physical
Christian Helke, Markus Reinhardt, Markus Arnold, Falk Schwenzer, Micha Haase, Matthias Wachs, Christian Gossler, Jonathan Goetz, Daniel Keppeler, Bettina Wolf, Jannis Schaeper, Tim Salditt, Tobias Moser, Ulrich Theodor Schwarz, Danny Reuter
Summary: Improved hearing restoration through optical cochlear implants, which excite optogenetically modified spiral ganglion neurons via an optical pulse, is achieved by using flexible polymer-based waveguide probes. These probes are fabricated using micromachining processes and are capable of guiding light with low intensity loss.
Article
Neurosciences
Victoria Hunniford, Robert Kuehler, Bettina Wolf, Daniel Keppeler, Nicola Strenzke, Tobias Moser
Summary: Hearing-impaired individuals using electrical cochlear implants (eCIs) expressed a desire for improved speech comprehension, music appreciation, and more natural sound impression. They showed willingness to engage with new technologies for improved hearing restoration. However, they had concerns about receiving an implant that had not been evaluated in a human clinical trial.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Otorhinolaryngology
Malak Salame, Crystel Bonnet, Ely Cheikh Mohamed Moctar, Selma Mohamed Brahim, Abdallahi Dedy, Ledour Abdel Vetah, Fatimetou Veten, Cheikh Tijani Hamed, Christine Petit, Ahmed Houmeida
Summary: In this study, the exon 7 of the LRTOMT gene was screened in a cohort of congenital deaf children from Mauritania, and a novel pathogenic mutation was identified. The mutation was found to disrupt the structure of the encoded protein and early cochlear implant fitting seemed to improve the auditory ability of the mutation carrier. Further screening of deafness genes may reveal other variants underlying hearing impairment in the population.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2023)
Article
Cell Biology
Anders Karlsen, Ching-Yan Chloe Yeung, Peter Schjerling, Linda Denz, Christian Hoegsbjerg, Jens R. Jakobsen, Michael R. Krogsgaard, Manuel Koch, Stefano Schiaffino, Michael Kjaer, Abigail L. Mackey
Summary: Through single-nucleus RNA sequencing, we identified distinct clusters of myonuclei in the myotendinous junction (MTJ) of humans, characterized by different gene expression profiles and fiber types, which has important implications for understanding the specialization of the MTJ.
JOURNAL OF CELL SCIENCE
(2023)
Review
Genetics & Heredity
Christine Petit, Crystel Bonnet, Saaid Safieddine
Summary: Progress in genetic studies of SNHI and multidisciplinary studies of mouse models have elucidated the molecular mechanisms underlying auditory system function, leading to the development of inner-ear gene therapy. Preclinical studies have highlighted key translational opportunities and challenges for treating monogenic forms of SNHI and associated balance disorders.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Philippe Jean, Fabienne Wong Jun Tai, Amrit Singh-Estivalet, Andrea Lelli, Cyril Scandola, Sebastien Megharba, Sandrine Schmutz, Solene Roux, Sabrina Mechaussier, Muriel Sudres, Enguerran Mouly, Anne-Valerie Heritier, Crystel Bonnet, Adeline Mallet, Sophie Novault, Valentina Libri, Christine Petit, Nicolas Michalski
Summary: Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. By analyzing the single-cell transcriptomic atlas of the mouse cochlea, researchers have identified almost all cochlear cell types and discovered three cell types, providing insights into the gene regulatory networks controlling cochlear cell differentiation and maturation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Markus Meier, Monika Gupta, Serife Akguel, Matthew McDougall, Thomas Imhof, Denise Nikodemus, Raphael Reuten, Aniel Moya-Torres, Vu To, Fraser Ferens, Fabian Heide, Gay Pauline Padilla-Meier, Philipp Kukura, Wenming Huang, Birgit Gerisch, Matthias Moergelin, Kate Poole, Adam Antebi, Manuel Koch, Joerg Stetefeld
Summary: In this study, the authors provide a molecular understanding of the interactions between netrin-1 and glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. They demonstrate that heparin oligosaccharides significantly impact the dynamic behavior of netrin-1, inducing the formation of unknown netrin-1 filaments. These findings contribute to a better understanding of the functions of netrin-1.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Melina Hussmann, Dorte Schulte, Sarah Weischer, Claudia Carlantoni, Hiroyuki Nakajima, Naoki Mochizuki, Didier Y. R. Stainier, Thomas Zobel, Manuel Koch, Stefan Schulte-Merker, Victoria L. Bautch
Summary: This study reveals the critical roles of Svep1 and Tie1 in the development of specific subpopulations of the zebrafish facial lymphatic network. It also shows that this aspect of the network is formed independently of Vegfc signaling. The findings demonstrate the importance of Tie1 signaling in lymphangiogenesis and blood vessel development in zebrafish.
Article
Medicine, Research & Experimental
Maria Zerche, Christian Wrobel, Kathrin Kusch, Tobias Moser, Thomas Mager
Summary: Optogenetic neurostimulation, using f-Chrimson-TSKir2.1 as a candidate, shows promise for sensory restoration and can be a potential alternative to electrical stimulation methods. Although removing the C-terminal fluorescent protein leads to a reduction in photocurrent amplitude, adjusting the dose of the adenoassociated virus vector and using the Kir2.1 trafficking sequence can restore optogenetic stimulation efficacy with minimal neural loss after a few months. This research holds significance for the clinical translation of optogenetic neurostimulation, particularly in the development of optical cochlear implants.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Cell Biology
Ines Klein, Jorg Isensee, Martin H. J. Wiesen, Thomas Imhof, Meike K. Wassermann, Carsten Mueller, Tim Hucho, Manuel Koch, Helmar C. Lehmann
Summary: Peripheral neuropathy is a common side effect of cancer treatment with paclitaxel, but the mechanisms of paclitaxel transport into neurons are not well understood. This study identified OATP1A1 and OATP1B2 as the primary neuronal transporters for paclitaxel and suggested that inhibiting these transporters may prevent paclitaxel-induced neuropathy.
Article
Genetics & Heredity
Isabelle Roux, Cristina Fenollar-Ferrer, Hyun Jae Lee, Parna Chattaraj, Ivan A. Lopez, Kyungreem Han, Keiji Honda, Carmen C. Brewer, John A. Butman, Robert J. Morell, Donna M. Martin, Andrew J. Griffith
Summary: Enlargement of the endolymphatic sac, duct, and vestibular aqueduct (EVA) is a common inner ear malformation in patients with hearing loss, and is associated with pathogenic variants in SLC26A4. However, in European-Caucasian populations, around 50% of EVA patients have no pathogenic alleles of SLC26A4. This study found that CHD7 variants can cause EVA and nonsyndromic hearing loss, and suggest that CHD7 should be included in DNA sequence analyses for EVA patients.
Article
Immunology
Maria Rafaeva, Adina R. D. Jensen, Edward R. Horton, Kamilla W. Zornhagen, Jan E. Strobech, Lutz Fleischhauer, Alejandro E. Mayorca-Guiliani, Sebastian R. Nielsen, Dina S. Gronseth, Filip Kus, Erwin M. Schoof, Luis Arnes, Manuel Koch, Hauke Clausen-Schaumann, Valerio Izzi, Raphael Reuten, Janine T. Erler
Summary: The desmoplastic reaction observed in many cancers, particularly in breast and pancreatic cancer, is a significant indicator of disease progression and prognosis. Alterations in stromal-derived extracellular matrix (ECM) within desmoplasia play a crucial role in driving cancer progression. Using fibroblast-derived matrices (FDMs), it was found that cancer cells have increased growth on cancer associated FDMs compared to FDMs derived from non-malignant tissue fibroblasts. Compositional, structural, and mechanical analyses revealed significant differences in ECM characteristics between normal and cancer-associated stroma at the primary tumor site.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Multidisciplinary Sciences
Lakshay Khurana, Tamas Harczos, Tobias Moser, Lukasz Jablonski
Summary: Hearing loss is a common sensory deficit, and optical cochlear implants have the potential to overcome the limitations of electrical implants by using light stimulation.
